What genetic data can a person with polydactyly (extra fingers or toes) explore to understand their condition better, given a family history of similar anomalies?

Genetic Testing for Polydactyly

Yes, genetic testing is available and useful for understanding polydactyly, with at least 10 genetic loci and six specific genes identified that cause non-syndromic polydactyly, including GLI3, ZNF141, MIPOL1, IQCE, PITX1, and GLI1. 1

Understanding Your Specific Case

Your presentation with two extra finger digits and one extra pinky toe represents postaxial polydactyly (extra digits on the ulnar/little finger side), which is the most common type of polydactyly and typically follows an autosomal dominant inheritance pattern with variable expressivity. 2, 1 This means:

• Only one copy of a mutated gene is needed to cause the condition 1
• The trait can "skip" generations or appear with different severity in different family members 3
• Up to 30% of cases can be de novo mutations (new mutations not inherited from parents), which explains why no other family members may be obviously affected 4
• The "weird toe that was shaved down and grew back" in your relative likely represents a mild form of the same genetic condition, demonstrating the variable expressivity within families 3, 5

Genetic Data You Can Pursue

First-Tier Testing Approach

Start with targeted gene panel testing focusing on the six known polydactyly genes: GLI3, ZNF141, MIPOL1, IQCE, PITX1, and GLI1. 1 These account for the majority of identified non-syndromic polydactyly cases and provide the highest diagnostic yield.

Why GLI3 and Related Genes Matter

GLI3 mutations are particularly important because they cause overlapping polydactyly phenotypes and are involved in controlling digit number during limb development. 2 Interestingly, GLI3 and the SHH signaling pathway (which includes the ZRS/SHH enhancer) are antagonistic factors that modulate digit formation, and mutations in either can produce similar extra digit patterns. 2

What Testing Will Reveal

Genetic testing provides:

• 100% specificity for established pathogenic mutations 4
• Confirmation of the specific gene involved 1
• Information about inheritance pattern for family planning 1
• Explanation for the variable presentation in your family (why the relative only had a "weird toe") 3

Important Caveats About Your Situation

The absence of obvious family history does not rule out genetic causation. 2, 1 Several factors explain this:

• Variable penetrance: Not everyone with the mutation shows obvious signs 3, 5
• Variable expressivity: The severity ranges from a small skin tag (like your relative's toe) to fully formed extra digits 3, 5
• De novo mutations: Your case could represent a new mutation 4
• Postaxial polydactyly type B (pedunculated/dangling extra digits) is often so mild it may go unnoticed or unreported in family histories 5

Clinical Significance

Postaxial polydactyly is isolated in 95% of cases and has no medical significance beyond cosmetic and functional considerations. 5 However, genetic testing is still valuable because:

• It confirms the diagnosis definitively 1
• It provides information for genetic counseling if you plan to have children 1
• It rules out syndromic forms that might require additional medical surveillance 6

Practical Next Steps

1. Consult a medical geneticist or genetic counselor who can order appropriate gene panel testing 1
2. Document your family history carefully, including that relative's toe abnormality, as this supports the hereditary nature 3
3. Consider testing the relative with the toe abnormality if they're willing, as this could help establish the familial pattern 3
4. Request comprehensive polydactyly gene panel testing rather than single-gene testing to maximize diagnostic yield 1

The substantial genetic heterogeneity in polydactyly across populations means comprehensive panel testing is more cost-effective than sequential single-gene testing. 2, 1